Composition and method for reducing food intake

ABSTRACT

The present invention features a composition and method for reducing food intake. The composition of the invention is composed of yerbe maté extract, guarana extract, and damiana extract in combination with a dietary fiber.

INTRODUCTION

This application is a continuation-in-part application of U.S.application Ser. No. 12/824,509 filed Jun. 28, 2010, which claimsbenefit of priority to U.S. Provisional Application Ser. No. 61/222,141,filed Jul. 1, 2009, the contents of which are incorporated herein byreference in their entireties.

BACKGROUND OF THE INVENTION

The necessary condition for the reduction of body mass is a negativeenergy balance. Energy intake must be consistently lower than energyexpenditure in order for weight loss to occur. Therefore, any weightcontrol strategy must address one or both parts of the energy equation;intake or expenditure. With regard to the control of energy intake, twobroad strategies can be adopted: the enhancement of the satiety responseto food or the blockade of absorption. The physical and chemicalproperties of various foods can be used to achieve both effects.

With specific regard to the modulation of appetite, those processesresponsible for the termination of a meal and the suppression ofsubsequent intake are of particular interest. The within meal processesof satiation and the post-meal end state of satiety are generated by thesensory, physical and chemical characteristics of the food consumed. Thestrength of these signals determines meal duration and meal size, andthe length of the post-meal interval before the next eating occasion.The activation of such signals can be employed to enhance the appetiteresponse to food and limit caloric intake.

Various naturally occurring ingredients including herbal extracts havebeen shown to produce beneficial effects on appetite and weight controlwhen used as supplements or food components (Ruxton, et al. (2005) Br.Food J. 107:111-125; Ruxton, et al. (2007) Br. Food J. 109: 416-428).ZOTRIM is a mixed herbal preparation containing Yerbe Maté, Guarana andDamiana, common ingredients of commercially available drinks, and theproduct is available in the UK as a food supplement. This herb extractformulation significantly delays gastric emptying, reduced the time toperceived gastric fullness and induced significant weight loss over 45days in overweight patients (Anderson & Fogh (2001) J. Hum. Nutr.Dietet. 14:243-250). A consumer study has also been undertaken to testthe efficacy of this preparation in the field. A total of 48 free-livingsubjects completed a 28-day trial and demonstrated a self-reported meanweight loss of 2.3 kg. Questionnaire data suggested that subjects ateless at meals and snacked less frequently (Ruxton (2004) Nutr. Food Sci.34:25-28; Ruxton, et al. (2005) Nut. Food Sci. 35:303-331; Ruxton, etal. (2007) supra). However, the effects of ZOTRIM on human food intake,feeding behaviour and subjective feelings of appetite and satiety werenot determined.

FIBRESURE is a 100% natural fiber supplement that can be taken daily.The term fiber covers a wide variety of substances belonging to thefamily of carbohydrates that resist hydrolysis by human alimentaryenzymes but are fermented by colonic micro flora (Bianchi & Capurso(2002) Dig. Liver Dis. 34(Suppl 2):S129-33). Fiber is normally connectedwith increases in satiety due to its high viscosity and bulking effect(Burton-Freeman (2000) J. Nutr. 130:272S-275S). However, FIBRESURE is afiber product with little effect on viscosity. Current recommendationsfor the management of obesity and diabetes mellitus include an increasein dietary fiber intake, as it may contribute to lower fasting andpostprandial plasma glucose concentrations and improvement of glycaemiccontrol, which can help control energy intake (Vinik & Jenkins (1988)Diabetes Care 11:160-173). FIBRESURE contains the soluble fiber inulin,which is a prebiotic carbohydrate derived from chicory root. Inulin andinulin-type fructans are mostly oligosaccharides or oligofructoses andstimulate colonic production of Short Chain Fatty Acids (SCFAs),(Guarner (2005) Brit. J. Nutr. 93:S61-5). Fiber fermentability whichproduces SOFA has been linked with increasing satiety (Bosch (2008) Br.J. Nutr. 102:318-325).

The mechanism by which inulin and inulin-type fructans exert a satiatingeffect has not been identified. There are many gastrointestinal peptidesthat affect food intake such as ghrelin, cholecystokinin (CCK),glucagon-like peptide-1 (7-36) amide (GLP-1), oxyntomodulin, peptide YY(PYY) and pancreatic polypeptide (PP). Fructans modulategastrointestinal peptides involved in the control of food intake,particularly GLP-1 and ghrelin (Orskov, et al. (1989) J. Biol. Chem.264(22):12826-12829). GLP-1 is an anorectic peptide secreted by theL-cells which suppresses meal-induced gastric acid and pancreatic juicesecretion and slows gastric emptying (Schjoldager, et al. (1989) Dig.Dis. Sci. 34:703-708). There are several studies showing that peripheralinjection of GLP-1 decreases food intake and consequently body weight inrats and human subjects, (Meier, et al. (2002) Eur. J. Pharmacol.440:269-279; Zander, et al. (2002) Lancet 359:824-830). Ghrelin isassociated with the mesolimbic cholinergic dopaminergic reward system.This reward link is composed of cholinergic input from the laterodorsaltegmental area to the mesolimbic dopamine system that originates in theventral tegmental area and projects to the nucleus accumbens (Jerlhag,et al. (2007) Addict. Biol. 12(1):6-16). In this respect, treatment ofhuman volunteers with approximately 20 g of oligofructose per day for 7days increased serum GLP-1 levels (Piche, et al. (2003) Gastroenterology124(4):894-902). Furthermore, in a study of 14 healthy volunteers, itwas found that the gut peptide GLP-1 decreases motility in theantro-duodeno-jejunal region thus inducing satiety (Hellstrom, et al.(2008) Neurogastroenterol. Motil. 20(6):649-59).

SUMMARY OF THE INVENTION

This invention is composition for suppressing appetite consistingessentially of about 336 mg of yerba maté leaf extract, about 285 mg ofguarana seed extract, about 108 mg of damiana leaf extract, about 5grams of isolated, fermentable inulin, vitamin B and vitamin C. Incertain embodiments, the composition is formulated as a tablet, sachet,solid food product, dairy product, breakfast cereal, muesli, candy,confectionery, cookie, biscuit, cracker, chocolate, chew, chewing-gum,dessert or liquid comestible.

DETAILED DESCRIPTION OF THE INVENTION

It has now been found that a combination of selected herbal extracts(i.e., yerbe maté extract, guarana extract, damiana extract) and dietaryfiber can significantly decrease food intake compared to use of theherbal extracts alone or dietary fiber alone. Specifically, thecombination of herbal extract and dietary fiber described hereinprovided a significant reduction in gram (91.4 g, 24.3%) and kcal intake(202.kcal, 26.7%) as compared to placebo-water. Further, the combinedadministration of herbal extract and dietary fiber produced asignificant reduction in gram intake compared to placebo in all foodgroups except low fat sweet items; intake of high fat savory items wasreduced by 18.5 g (27.6%), low fat savory intake reduced by 19.1 g(13.6%) and the greatest reductions were seen for high fat sweet itemswhere intake was reduced by 31.1 g (48.8%). The study hereindemonstrated a significant and robust effect on food intake of astandard ad libitum lunch. Accordingly, the present invention features acomposition composed of yerbe maté extract, guarana extract, damianaextract and a dietary fiber for use in reducing food consumption and/orcalorie intake.

As is conventional in the art, appetite is a natural desire, or longingfor food. According to the present invention, increased appetitegenerally leads to increased feeding behaviour. In this respect, anappetite suppressant is a composition that decreases the desire forfood, as evidenced by a decrease in food consumption and/or calorieintake.

The composition of the present invention is composed of soluble extractsof yerbe maté (leaves of Ilex paraguayensis, I. vomitora, or I. dahoon),guarana (seeds of Paullinia cupana or P. sorbalis) and damiana (leavesof Turnera diffusa var. aphrodisiaca, T. opifera, or T. ulmifoliei).Soluble extracts of the invention can be prepared by conventionalmethods of drying and/or grinding plant biomass and subjecting the sameto one or more suitable solvents, thereby providing an extract, whichmay be either used as a crude extract or further fractionated.

Suitable methods for drying plant biomass include: sun drying followedby a heated air-drying or freeze-drying; lyophilization or chopping thebiomass into small pieces, e.g., 2-10 cm, followed by heated air-dryingor freeze-drying. Once sufficient moisture has been removed, e.g., morethan 90%, the material can be ground to a coarse particle size, e.g.,0.01-1 mm, using a commercial grinder. For laboratory scale extraction,a coffee grinder or equivalent can be used.

In general terms, a suitable method for preparing an extract of plantbiomass includes the steps of treating collected plant biomass with asolvent to extract a fraction having appetite suppressant or curbingactivity, separating the extraction solution from the rest of the plantbiomass, removing the solvent from the extraction solution andrecovering the extract. The extract so recovered may be further purifiedby way of suitable extraction or purification procedures.

More specifically, plant biomass can be ground to a coarse powder asdescribed above. Subsequently, a suitable solvent, e.g., a food gradesolvent, can be added to the powder. A good grade solvent is any solventwhich is suitable and approved for use in conjunction with foodsintended for human consumption. Examples of suitable solvents arealcohol-based solvents, ethyl acetate, liquid carbon dioxide, hexane,and one or more components of fusel oil, e.g., ethyl acetate.Alcohol-based solvents, i.e., pure alcohol solvents and mixtures thereofwith water or other organic solvents, are most desirable.

The extraction solution can then be separated from the residual plantbiomass by an appropriate separation procedure such as filtration and/orcentrifugation. The solvent can be removed, e.g., by means of a rotaryevaporator. The separated crude extract can then be tested to confirmappetite suppressant or appetite curbing activity in a suitable in vivobioassay.

A suitable and accepted in vivo model for measuring appetite suppressionor appetite curbing activity in an animal model is described in Example2. A clinically effective and medically approved anti-obesity drug,e.g., sibutramine, can be used as a positive control for reduction infood intake in this model. Positive results from this test model are anindicator of clinical efficacy in the human context. Alternatively,suppression, reduction or curbing of appetite can be assessed by any ofthe methods referred to in WO 98/46243.

Plant extracts of the invention can be dried to remove moisture, e.g.,by spray-drying, freeze-drying or vacuum-drying, to yield a free-flowingpowder. Optionally, the extracts can be dried on a pharmaceuticallyacceptable carrier, such as maltodextrin or starch. As yet a furtheralternative, plant biomass can be extracted and concentrated withoutdrying to give a liquid extract, which is effective in curbing orsuppressing appetite.

In addition to yerbe maté, guarana and damiana extract, the compositionof the invention can further include one or more of: extracts from theleaves of Buchu (Barosma betulina, B. crenulata, B. serratifolia)containing diosphenol (buchu camphor); extracts from the leaves orflowers of Vervain (Verbena officinales, V. jamaicensis, V. lappulacae,V. hesitate, V. urticifolia, V. Sinuata) containing glycosides,adenosine, essential oils, tannin, livertin and/or emulin; extracts ofKola nut (Cola nitida, C. vera) containing caffeine; or extracts fromthe leaves or flowers of Ginseng (Panax ginseng, P. quinquefolius L.)containing triterpenoid saponins.

In addition to herbal extracts, the present composition also features adietary fiber. As used herein, dietary fiber is the indigestible portionof plant foods that pushes food through the digestive system and absorbswater. Dietary fiber can be soluble (able to dissolve in water) orinsoluble (not able to dissolve in water). Soluble fiber, like allfiber, cannot be digested. But it does change as it passes through thedigestive tract, being transformed or fermented by bacteria therein. Incontrast, insoluble fiber passes through the body largely unchanged.Accordingly, in particular embodiments of the present invention, thedietary fiber is fermentable or soluble.

Fermentable dietary fiber can be obtained from a variety of plant foods,including, but not limited to legumes (e.g., peas, soybeans, and otherbeans); grains such as oats, rye, chia, and barley; some fruits andfruit juices including prune juice, plums, berries, bananas, and theinsides of apples and pears; certain vegetables such as broccoli,carrots and Jerusalem artichokes; root vegetables such as potatoes,sweet potatoes, and onions; and psyllium seed husk. In particularembodiments, the dietary fiber is isolated and/or substantially purifiedto homogeneity, e.g., at least to 75%, 80%, 85%, or 90%, homogeneity orup to 99% homogeneity.

For use in accordance with the present invention, the isolated,fermentable dietary fiber is inulin, a beta-glucan, a pectin, a naturalgum, an oligosaccharide, psyllium seed husk, a resistant dextrin, analginate or a combination thereof. Inulin, belonging to the class offibers known as fructans, is typically extracted from enriched plantsources such as chicory roots or Jerusalem artichokes. Beta-glucans,polysaccharides of D-glucose monomers linked by glycosidic bonds, aretypically isolated from oat bran, whole oats, oatrim or rolled oats.Pectins, a complex set of polysaccharides that are present in mostprimary cell walls and particularly abundant in the non-woody parts ofterrestrial plants, are composed of a linear chain of α-(1-4)-linkedD-galacturonic acid that forms the pectin-backbone. Natural gums, whichare polysaccharides of natural origin that are capable of causing alarge viscosity increase in solution, include, but are not limited toxanthan gum, acacia gum or guar gum. Alginate is a soluble fiberextracted from seaweed. According to the present invention,oligosaccharides, saccharide polymers containing a small number(typically three to ten) of component sugars (also known as simplesugars), particularly include fructooligosaccharides. As is conventionalin the art, a resistant dextrin is a water-soluble dietary fiberobtained by, e.g., subjecting starch to high-temperature heating andenzymatic hydrolysis with α-amylase and glucoamylase. The selection ofthe dietary fiber to be used in the composition of the present inventioncan be dependent upon the form of the composition and the manner inwhich the formulation is administered, e.g., as multiple differentformulations or as one formulation containing yerbe mate extract,guarana extract, damiana extract and dietary fiber. In particularembodiments, the dietary fiber of the instant composition is inulin.

According to this invention, the herbal extracts and dietary fiber canbe provided as a composition prepared as individual formulations (e.g.,the composition includes or comprises a formulation containing yerbemate extract, a formulation containing guarana extract, a formulationcontaining damiana extract, and a formulation containing a dietaryfiber), or the composition can be prepared as a combination offormulations (e.g., the composition includes or comprises a formulationcontaining yerbe maté extract, guarana extract, and damiana extract; anda formulation containing a dietary fiber), or the composition can beprepared as a single unitary formulation (e.g., the composition includesor comprises a formulation containing yerbe maté extract, guaranaextract, damiana extract, and dietary fiber). Moreover, when thecomposition is prepared as individual or a combination of formulations,said formulations can be the same, e.g., all tablets; or different,e.g., a capsule formulation and a liquid formulation. In addition, whentaken as individual formulations, said formulations can be takensimultaneously or consecutively, e.g., within minutes of each other.

Soluble plant extracts, dietary fiber or a combination thereof can beadmixed by conventional compounding procedures with any conventionalpharmaceutical or nutritionally acceptable excipient, diluent or carrierin the preparation of pharmaceuticals, nutraceuticals, nutritionalcompositions, such as dietary supplements, slimming compositions,medical nutrition or functional foods. Typically, this involves mixingthe active ingredients of the invention together with ediblepharmaceutically or nutritionally acceptable solid or liquid carriersand/or excipients, e.g., fillers, such as cellulose, lactose, sucrose,mannitol, sorbitol, and calcium phosphates; and binders, such as starch,gelatin, tragacanth, methylcellulose and/or polyvinylpyrrolidone (PVP).Optional additives include lubricants and flow conditioners, e.g.,silicic acid, silicon dioxide, talc, stearic acid, magnesium/calciumstearates and polyethylene glycol (PEG) diluents; disintegrating agents,e.g., starch, carboxymethyl starch, cross-linked PVP, agar, alginic acidand alginates, coloring agents, flavoring agents and melting agents.Dyes or pigments may be added to tablets or dragee coatings, forexample, for identification purposes or to indicate different doses ofactive ingredient.

The composition of the invention can optionally include conventionalfood additives, such as any of emulsifiers, stabilizers, sweeteners,flavorings, coloring agents, preservatives, chelating agents, osmoticagents, buffers or agents for pH adjustment, acidulants, thickeners,texturizers and the like.

Suitable product formulations according to the present invention includesachets, soft gel, powders, syrups, pills, capsules, tablets, liquiddrops, sublinguals, patches, suppositories, and liquids. Alsocontemplated are food and beverage products containing the compositionof the present invention, such as solid food products, like bars (e.g.,nutritional bars or cereal bars), powdered drinks, dairy products,breakfast cereals, muesli, candies, confectioneries, cookies, biscuits,crackers, chocolate, chews, chewing-gum, desserts and the like; liquidcomestibles, like soft drinks, juice, sports drinks, milk drinks,milk-shakes, yogurt drinks or soups, as well as pet treats, pet foods,etc.

The composition of the invention can be provided as a component of anormal meal, e.g., a nutritional or slimming composition, or dietarysupplement, in the form of a health drink, a snack or a nutritionallyfortified beverage, as well as a pill, a tablet or a softgel, forexample. When used as a snack or dietary supplement it will preferablybe consumed between or before meals.

Optionally, the composition according to the invention can benutritionally complete, i.e., may include vitamins, minerals, traceelements as well as nitrogen, carbohydrate and fatty acid sources sothat it may be used as the sole source of nutrition supplyingessentially all the required daily amounts of vitamins, minerals,carbohydrates, fatty acids, proteins and the like. Accordingly, thecomposition of the invention may be provided in the form of anutritionally balanced complete meal, e.g., suited for oral or tubefeeding.

In addition to the herbal extracts and dietary fiber, the composition ofthe invention may also include one or more further active ingredients,e.g., capsaicin (red pepper); fatty acids, especially linoleic acid (LA)and conjugated linoleic acid (CLA); glycomacropeptide (GMP); Long ChainTriglyceride (LCT); enterostatin; galactose; glucuronic acid;hydroxycitrate (HCA); citrus; β-hydroxy butyrate; medium chaintryglycerides (MCTs); D-tagatose; caffeine; potato extract; green teaextract; epigallocatechin gallate, or other catechins; peptide D4;vitamins B (e.g., Vitamin B3 and/or B6), C and/or E; and chromiumpicolinate. By way of illustration, the composition can include about6.9 mg Vitamin B3, 0.84 mg Vitamin B6 and/or 20 mg Vitamin C.Alternatively, the composition of the invention may be combined with ananti-obesity drug, such as sibutramine. For example, the composition ofthe invention may be provided in the form of a kit for separate,sequential or simultaneous administration in conjunction with ananti-obesity drug such as orlistat (XENICAL™), Hoodia extract, and thelike.

Daily dosage of a composition of the present invention would usually besingle or multiple servings per day, e.g., once or twice daily, foracute or chronic use. However, benefit may be derived from dosingregimens that can include consumption on a daily, weekly or monthlybasis or any combination thereof. Administration of compositions of theinvention, e.g., treatment, could continue over a period of days, weeks,months or years, in order, for example, to constantly control theweight, or until a healthy or cosmetically beneficial loss of bodyweight has occurred. Optimally, the composition of the invention isconsumed at least once a day on a regular basis, prior to (i.e.,pre-prandial administration), or during a meal. Preferably, thecomposition of the invention is consumed prior to a meal.

The amount and dosage regimen of the composition of the invention to beadministered is determined in the light of various relevant factorsincluding the purpose of administration, the age, sex and body weight ofan individual subject, i.e., inter alia on the severity of the subject'sobesity or overweight. In this respect, the compositions of theinvention can be administered under the supervision of a medicalspecialist, or may be self-administered.

Preferred delivery formats for the appetite suppressing or appetitecurbing composition of the invention, would be as a dietary supplementcontaining about 50 mg to about 150 mg, or preferably about 100 mg toabout 120 mg, dry weight of yerbe maté extract; about 50 mg to about 120mg, or preferably about 90 mg to 100 mg, of gaurana extract; about 20 mgto about 50 mg, or preferably about 30 mg to about 40 mg, of damianaextract; and about 2 grams to about 10 grams, or preferably about 5grams to 7 grams, of dietary fiber.

An illustrative example of a formulation of herbal extracts is 27.5%weight yerbe maté extract, 23.2% weight Guarana, 9% weight Damianaextract, and 40.3% weight of dicalcium phosphate, talc, sodiumcarboxymethylcellulose, magnesium stearate andhydroxypropylmethylcellulose as additional ingredients.

The present invention also features a method for decrease food intakeand/or suppressing appetite by administering to a subject in needthereof an effective amount of yerbe maté extract, guarana extract, anddamiana extract in combination with a dietary fiber. Administration ofthe composition of the present invention results in a 10% to 40%decrease in food consumption (gram weight) or a 10% to 35% decrease incalorie intake (Kcal) as compared to a subject not receiving thecomposition. In particular embodiments, the composition of the presentinvention achieves a 20 to 30% reduction in food consumption or calorieintake, levels which unexpectedly surpass other nutritional weight losscompositions. For example, while humans studies analyzing the effects ofCaralluma fimbriata have shown a 8.2% reduction in energy intake(Kuriyan, et al. (2007) Appetite 48:338-344), human studies of sodiumalginate showed a 7% reduction in energy intake (Paxman, et al. (2008)Appetite 51:713-719), human studies of oligofructose (solublefermentable non-viscous fiber) have shown a 5% reduction in total intake(Cani, et al. (2006) Euro. J. Clin. Nutr. 60:567-572), and human studiesof hydroxycitric acid (HCA-SX) and a combination of HCA-SX andniacin-bound chromium (NBC) and Gymnema sylvestre extract (GSE) haveshown a 4% decrease in food intake (Preuss, et al. (2004) Nutr. Res.24:45-58), human studies with a natural dietary compound of chromiumpicolinate, inulin, capsicum, L-phenylalanine, and other lipotropicnutrients has not shown any significant difference in energy intake(Hoeger, et al. (1998) Adv. Ther. 15:305-14). Similarly, food intake andappetite ratings were not significantly reduced when either beta-glucanand fructooligosaccharides are used alone or in combination (Peters, etal. (2009) Am. J. Clin. Nutr. 89:58-63; Kim, et al. (2006) Cer. FoodsWorld, pg. 29), or with a fiber system of alginate and guar gum (Mattes(2007) Physiol. Behav. 90:705-711), or with supplements of fermentablefibers (pectin, beta-glucan) and non-fermentable methylcellulose(Howarth, et al. (2003) J. Nutr. 133:3141-3144). Indeed, the levels ofreduction in food/calorie intake of the instant composition are morecomparable to pharmacological options including sibutramine (12-26%reduction; Rolls, et al. (1998) Obes. Res. 6:1-11; Chapelot, et al.(2000) Physiol. Behav. 68:299-308), diethylpropion (11-15% reduction;Porikos, et al. (1980) Clin. Pharmacol. Ther. 27:815-822), fluoxetin(13-16% reduction; McGuirk & Silverstone (1990) Int. J. Obes. 14:361-72)and fenfluramine/d-fenfluramine (17-22% reduction; Goodall & Silverstone(1988) Appetite 11:215-288. See, also, Halford, et al. (2007) Drugs67:27-55 and Halford, et al. (2004) Curr. Drug Targets 5:221-40.

Subjects benefiting from the method of the invention include those inneed of weight loss, e.g. overweight or obese subjects, as well assubjects controlling food intake so as not to gain weight. In someembodiments, subjects receiving the composition of this invention areaverage or slightly overweight, i.e., having a BMI of 18.5-29.9 kg/m².In other embodiments, subjects receiving the composition of thisinvention are overweight, i.e., having a BMI of greater than 29.9 kg/m².In further embodiments, subjects benefiting from the method of theinvention are those that consume high fat food, e.g., food containinggreater than 8 g of fat per 100 g.

In addition to the uses described therein, the invention furtherprovides a composition according to the invention for use in suppressingappetite.

The invention additionally provides the use of yerba mate extract,guarana extract, daminiana extract and a dietary fiber in themanufacture of a composition for suppressing appetite.

The invention is described in greater detail by the followingnon-limiting examples.

Example 1: Materials and Methods

Study Design.

This was a double-blind, placebo-controlled study using a randomizedwithin-subject design to evaluate the effects of ZOTRIM and inulin fibergiven together, separately and against placebo control in terms of foodintake in grams and kilocalories and subsequent food ratings measuredusing visual analogue scales (VAS) of hunger, fullness, prospectiveconsumption, desire to eat and satisfaction pre dosing, pre and postmeals and at hourly intervals across the day. The independent variableswere the four conditions—ZOTRIM (tablet form) and inulin fiber (powdermixed with water), ZOTRIM and control, inulin fiber and placebo andcontrol and placebo. The dependant variables were food intake measuredin grams, kilocalories and macronutrients and the VAS ratings. All foodand water was recorded by weight scales (Sartorius Model CPA 4202S,Sartorius Ltd, Epsom, UK; 0.1 gram accuracy) before and after meals toascertain intake in grams, kilocalories and macronutrients, and foodchoice. There were two VAS's: the first was given nine times throughoutthe study day and measured hunger, fullness, prospective consumption,desire to eat, satisfaction, nausea and thirst. The second VAS measuredpleasantness, palatability, tastiness, saltiness and sweetness and wasgiven after breakfast and lunch. The product/placebo was administered 15minutes before breakfast and lunch which were four hours apart.Participants were randomized to the study by means of a block plancreated on an internet-based randomization program.

Participants.

Fifty-eight healthy, average and slightly overweight (body mass index[BMI]: 18.5-29.9 kg/m²) women completed the study. Volunteers wererecruited by advertisement. Upon response to the advertisements,individuals completed a standardized telephone or email interview toassess their age, height, weight, occupation, smoking status and abilityto attend the study center at the requisite times. Those who were agedover 65, with a BMI<18.5 kg/m² or >29.9 kg/m², who disliked more than25% of the ad-libitum lunch study foods, were smokers, currentlydieting, or who did not eat regular meals, were not studied further.

Initial Screening.

Following the initial telephone/email interview, potential participantsreceived detailed information on the protocol, and were invited to thestudy center, (The Kissileff Laboratory for the Study of IngestiveBehaviour in the School of Psychology, The University of Liverpool), fora full screening no more than 21 days before commencing the study. Allvolunteers signed an informed consent before any study-specificprocedures were undertaken. Confidentiality and anonymity were assured.

At screening, the following measurements were taken: height measuredwithout shoes, using a stadiometer to the nearest cm and weight usingstandard calibrated scales to the nearest 0.1 kg. Participants alsocompleted a medical history, diet history, and eating behaviourquestionnaire (The Dutch Eating Behaviour Questionnaire [DEBQ-R]).

Exclusion Criteria.

Following screening, participants were excluded from the study if theyreported any of the following: significant health problems; not havingdieted in the last 12 months to lose or control weight; currentlyadhering to a specific food avoidance diet; gastrointestinal symptomsrequiring treatment; bariatric surgery; systemic or local treatmentlikely to interfere with evaluation of the study parameters; takingmedication known to affect appetite or weight within the past monthand/or during the study; pregnant or planning to become pregnant orbreastfeeding; history of anaphylaxis to food; general or specific foodallergies, including caffeine and any of the study foods; dislike ofmore than 25% of the ad-libitum study foods; extreme dietary restraint;non breakfast eaters; working in nutrition, dietetics, food research,food manufacturing or supplements industry.

Those participants who fulfilled the study criteria were recruited tothe study and assigned a code number.

Study Supplement.

The ZOTRIM formulation contained 112 mg Yerbe Mate, 95 mg Guarana and 36mg Damiana. Guarana, a dough made from the seeds of Paullinia cupana,which grows in Brazil and Venezuela, contains 3-6% caffeine, 5-8.5%tannins, 7.8% resins, 2-3% lipid, 0.06% saponin, 5-6% starch and 1.5%coloring agents (Schery (1954) Plants for Man. London: George Allen andUnwin, pp. 518-519). Yerbe Maté is an extract of Ilex paraguayensis fromBrazil, Argentina and Paraguay containing 1-1.5% caffeine, 4-10% tanninsand 3% resins and lipids (Hill (1952) Economic Botany. New York:McGraw-Hill Book Company, pp. 479-481.). Damiana is obtained from theleaves of the plant Turnera diffusa var. aphrodisiaca from California,Mexico, Brazil and Bolivia and contains ethereal oils, resins andtannins (Bradley (1992) British Medical Compendium, Vol. 1. London:British Herbal Medical Association, pp. 71-72.).

The placebo contained lactose and other ingredients minus the activeingredients. ZOTRIM and placebo were supplied as individual tablets andpackaged in coded containers labeled A or B to ensure the double-blindstatus of the study. All capsule components (active and inertingredients) were those approved and commonly used for commercialsupplements and health ingredients and produced by a commercial capsulemanufacturer. The inulin fiber (FIBRESURE) was derived from chicory rootand packaged in powder form in 5.8 g individual stick packs, containing5 g fiber per pack. Each dose of 5 grams of fiber was mixed into 100grams of water.

Participants were instructed to take the dose of 3 tablets with a glassof water (100 g) 15 minutes before their two main meals of each day. Theorder of treatments was counter-balanced across the four treatmentconditions, with inulin being mixed in or not mixed into the wateraccording to condition.

Materials and Tools.

VAS were used to rate degree of hunger, fullness, satisfaction, desireto eat, perception of how much participants could eat (prospectiveconsumption), thirst and nausea. VAS was composed of 100 mm horizontallines anchored by “not at all” and “extremely” at opposite ends, uponwhich participants record with a vertical line their subjective ratings.For example, hunger was rated along a 100 mm line that was preceded bythe question “how hungry do you feel at this moment?” and anchored onthe left by “not at all hungry” and on the right by “extremely hungry”,or “how pleasant was the breakfast?” being anchored on the left by “notat all pleasant” and on the right by “extremely pleasant”.

Participants completed these ratings nine times (T1-T9) during each testday. The exact times were: pre dose pre breakfast (T1), pre breakfast(T2), post breakfast (T3), Interval 1(T4), Interval 2 (T5), Interval 3(T6), pre dose pre lunch (T), pre lunch (T8), and post lunch (T9)Pleasantness VAS were completed at two time points, viz; post breakfastand post lunch.

Procedure.

At the screening visit, participants were asked if they had read andunderstood the information sheet concerning the study (which they weresent a minimum of two days before the screening visit). Participantswere then asked to sign two copies of the consent form. Participants'height and weight were measured. BMIs were calculated ensuring they werein a suitable range for the study. Participant's medical history andweight control history were taken. A DEBQ and list of study foods wereshown to the participants to ensure that they did not have anyobjections or intolerances to the study foods. Following the screening,participants were contacted to determine whether or not they were ableto continue in the study. Successful participants then received aninformation pack which contained details of their agreed times to visitthe lab. Participants were asked to fill in an evening food and activitydiary prior to attending the visits.

Visit two took place at a minimum of two days after screening.Subsequent visits took place as soon as possible leaving two daysbetween visits (giving a total of four visits). Breakfast was servedbetween 8:30 AM and 9:45 AM (time depending on when researcher andparticipant had arranged to meet at lab). If participants failed toattend their visit within these time limits, their session wasrescheduled for another day.

The protocol for the laboratory visits (four in total) was as follows:On the day preceding each study day participants were asked to keeptheir food intake, fluid intake and activity levels similar and not toconsume any alcohol. On each pre-study evening participants wererequested to record in a diary the food and drink they consumed and theactivities they undertook from 5:00 PM until they retired for the night.They were asked not to eat or drink anything except water from 12:00midnight until they attended at the study center the following morning.

At 8:30 AM on each study day participants attended the study center. Thediary was collected and participants were given instructions oncompleting the VAS, before filling in the first set of VAS ratings (T1).The pre-breakfast dose of product/placebo and a glass containing 100 mlwater were presented to the participant 15 minutes before breakfast.They were instructed to consume all of the tablets with all of thewater. They were weighed and details of compliance were recorded.Participants were then seated in the testing area in individualcubicles. After completing the pre-breakfast VAS ratings (T2),participants were given a fixed-load breakfast as shown in Table 1, andwere asked to consume everything presented within 20 minutes. Afterbreakfast, participants completed a post-breakfast set of VAS appetite(T3) and pleasantness ratings, and were then free to leave the studycenter. They were instructed not to eat or drink anything except waterthat was provided by the study. They were asked to complete VAS ratingsat hourly intervals (T4, T5 and T6) and to return to the study centerthree hours and forty minutes after their first dose was given to ensuretheir second dose would be given on time. On their return, the VASmeasures and remaining water (if any) were collected for assessment anda pre-dose VAS (T7) was completed. Fifteen minutes before lunch was tobe served (four hours after breakfast had been served) the studyproduct/placebo was presented with a glass containing 100 ml water andparticipants were instructed to swallow all of the tablets with all ofthe water.

TABLE 1 Amount Food* (g) % Kellogg's Cornflakes 30 Semi-skimmed UHT Milk125 Orange Juice 200 Sliced White Bread 60 % Energy from 10 (toasted)Protein Flora Margarine 10 % Energy from 17 Fat Strawberry Jam 20 %Energy from 73 Carbohydrate TOTAL WEIGHT 445 TOTAL KCALS 496 *Alsoincluded hot drink, 35 g milk and sugar if required.

A 15-minute rest period followed, during which the participants remainedin the study center. They then completed another VAS (T8) and wereserved an ad-libitum lunch as detailed in Table 2. Participants wereinstructed to eat as much as they liked from the choice of foods andwater offered, taking as long as they wished, and signaling when theyhad finished. Immediately following ad-libitum consumption of the testmeal, participants completed a set of post-lunch VAS ratings (T9).

Participants were then free to leave the study center. All food andwater was weighed (Sartorius Ltd) to the nearest 0.1 g before and aftereach meal to determine intake. The length of each meal was timed by thestudy staff although participants were only instructed there was a timelimit (of 20 minutes) at breakfast. After completion of the studyparticipants were debriefed and were reimbursed for their time andtravel expenses (if any).

Test Meals.

A standard fixed-load breakfast (496 kcal) was dispensed to participantsin all conditions (Table 1). In addition to the fixed-load breakfast, atthe first visit, participants were offered a hot drink of tea or coffeewith additional milk (35 g) and sugar if desired. If requested, thisdrink had to be consumed on each subsequent visit. The amount and energycomposition of the ad-libitum cold test lunch items is listed in Table2. The protein, carbohydrate and fat content of each test lung item arerespectively listed in Tables 3-5. This meal was designed to offer aselection of high and low fat savory and sweet food items. Water (500ml) was offered at the test meal. Participants were instructed to eat asmuch as they wished and to signal via a booth-based buzzer when they hadfinished.

TABLE 2 Amount Kcal/ Kcal in Food (g) 100 g Serving Tesco Medium SlicedWhite Bread 144.00 240.00 345.60 Flora 40.00 531.00 212.40 TescoSandwich Turkey 62.50 110.00 68.75 Tesco Danish Salami 44.60 495.00220.77 Tesco Medium Grated Cheddar 100.00 415.00 415.00 Cucumber 80.0010.00 8.00 Walkers Ready Salted Crisps 25.00 530.00 132.50 QuakerSnack-a-jacks S&V 30.00 410.00 123.00 Tesco Value Cookies 100.00 515.00515.00 Tesco Chocolate Mousse 62.50 200.00 125.00 Tesco Value FruitCocktail 410.00 46.00 188.60 Tesco Jelly Babies 120.00 368.00 441.60Total 2796.22

TABLE 3 Protein/ Protein in Food 100 g Serving Tesco Medium Sliced WhiteBread 8.20 11.81 Flora 0.00 0.00 Tesco Sandwich Turkey 21.20 13.25 TescoDanish Salami 13.20 5.89 Tesco Medium Grated Cheddar 24.40 24.40Cucumber 0.70 0.56 Walkers Ready Salted Crisps 6.50 1.63 QuakerSnack-a-jacks S&V 6.50 1.95 Tesco Value Cookies 4.80 4.80 TescoChocolate Mousse 3.50 2.19 Tesco Value Fruit Cocktail 0.40 1.64 TescoJelly Babies 2.30 2.76 Total 70.87

TABLE 4 Carbohydrate/ Carbohydrate in Food 100 g Serving Tesco MediumSliced White Bread 47.80 68.83 Flora 0.00 0.00 Tesco Sandwich Turkey0.80 0.50 Tesco Danish Salami 7.00 3.12 Tesco Medium Grated Cheddar 1.401.40 Cucumber 1.50 1.20 Walkers Ready Salted Crisps 49.00 12.25 QuakerSnack-a-jacks S&V 77.00 23.10 Tesco Value Cookies 65.00 65.00 TescoChocolate Mousse 26.80 16.75 Tesco Value Fruit Cocktail 11.00 45.10Tesco Jelly Babies 89.80 107.76 Total 345.01

TABLE 5 Fat/ Fat in Food 100 g Serving Tesco Medium Sliced White Bread1.50 2.16 Flora 59.00 23.60 Tesco Sandwich Turkey 2.30 1.44 Tesco DanishSalami 46.00 20.52 Tesco Medium Grated Cheddar 34.40 34.40 Cucumber 0.100.08 Walkers Ready Salted Crisps 34.00 8.50 Quaker Snack-a-jacks S&V8.00 2.40 Tesco Value Cookies 26.10 26.10 Tesco Chocolate Mousse 8.405.25 Tesco Value Fruit Cocktail 0.00 0.00 Tesco Jelly Babies 0.00 0.00Total 124.44

Lunch time was fixed at precisely 4 hours after breakfast. All mealswere served in individual booths in the test study center.

Adverse Events.

If participants reported any adverse events they had experienced whiletaking the study supplement the type, severity, date of onset andresolution were recorded.

Statistical Analysis.

Analysis was performed using SPSS for WINDOWS, Version 16 (SPSS Inc.,Chicago, US). Analysis of variance (ANOVA) and post-hoc paired t-testswere used. The assumptions of the ANOVA model were tested and ifhomogeneity of variance was not found, multivariate tests were adoptedfor that variable. All tests were two-tailed unless stated. Bonferronicorrections were applied for multiple comparisons.

Intake at the test meal was initially analyzed for amount consumed (ingrams and kcal) using a two-way ANOVA with condition (inulin fiber andZOTRIM) as within-subject factors. Because breakfast was fixed, this wasnot included in the statistical analysis. Paired t-tests were used toinvestigate any significant differences. This analysis was then re-runincorporating the kcal content of breakfast and the kcal content in theinulin fiber conditions. A two-way ANOVA with inulin and ZOTRIM aswithin subject factors was performed to analyze food choice at the testmeal. Kcal intake of high and low fat savory and high and low fat sweetitems were compared between conditions.

Subjective parameters (e.g., hunger, gastric fullness) rated on the VASwere analyzed using a within-subjects repeated measures ANOVA withcondition (ZOTRIM and placebo) and time (pre-dose pre-breakfast,pre-breakfast, post-breakfast, 10 AM, 11 AM, 12 PM, pre-dose pre-lunch,pre-lunch, post-lunch, 2 PM, 3 PM, 4 PM, and 5 PM; T1-T13) aswithin-subject factors. If a time-by-condition interaction effect wasfound significant, paired t-tests were conducted at each rating timebetween conditions.

Example 2: Herbal Extracts and Inulin Decrease Food Intake

Fifty-eight healthy average to slightly overweight women were recruitedto the study through advertising. A double blind, placebo-controlled,cross-over design was employed. After screening, eligible participantswere invited to the laboratory on four separate occasions for breakfastand lunch. The study days were arranged according to the participants'availability and always leaving a minimum of two days between eachvisit. On study days, the participants were administered the first doseof ZOTRIM and inulin fiber (5.8 g), ZOTRIM and water, inulin fiber andplacebo or water and placebo, 15 minutes before a fixed load breakfast.Four hours after the initial dose, and 15 minutes before lunch, thesecond dose of the same condition was given. The dose was composed ofthree tablets, either ZOTRIM (a dose having 336 mg of yerba mate leafextract, 285 mg of guarana seed extract and 108 mg of damiana leafextract) or a placebo, and a hundred grams of water into which inulinfiber was or was not mixed according to condition. Participants werethen offered an ad-libitum buffet lunch and the intake of each item oflunch was measured. Appetite was assessed using VAS.

In total 71 participants were screened, 62 were recruited and 58completed the study. Nine participants were excluded, six as their BMIwas >29.9, two due to medication they were taking and one as her BMI was<18.5. Of the four that were recruited to the study but did not completeit, three could not fit the visits around previous commitments and onecould not be contacted after her first visit. Their data has beenexcluded from analysis.

The demographic (age), and anthropometric (weight, height, BMI)characteristics of the completing participants are shown in Table 6.

TABLE 6 Mean (±SD, n = 58) Age (years) 21.31 ± 3.79 Weight (kg) 60.16 ±6.09 Height (m) 166.24 ± 5.23  Body Mass Index (BMI) [kg/m²] 21.78 ±1.99 DEBQ  2.56 ± 1.92

Intake at Test Meal.

Total mean number of grams (g) and kilocalories (kcal) consumed in eachcondition are displayed in Table 7.

TABLE 7 Mean Intake Mean Intake Number in Grams in Kilocalories (N) (g)(±SD) (kcal) (±SD) Condition A 58 375.60 752.14 (placebo) (±138.46)(±296.27) Condition B 58 328.96 619.94 (ZOTRIM) (±177.20) (±263.51)Condition C 58 356.50 662.30 (FIBRESURE) (±144.38) (±311.69) Condition D58 284.20 549.78 (ZOTRIM and (±105.47) (±182.16) FIBRESURE)

Gram Intake.

A 2×2 repeated measures ANOVA demonstrated a significant main effect ofZOTRIM on gram intake (F(1, 57)=26.110, p<0.001). The ANOVA alsodemonstrated a significant main effect of inulin fiber on gram intakeacross conditions, (F(1, 57)=12.661, p=0.001). There was no interactionbetween ZOTRIM and fiber conditions (F(1, 57)=1.841, p=0.180) on gramintake.

Paired samples t-tests showed that there was a significant reduction ingram intake from control of 46.6 grams (12.4%) in the ZOTRIM condition(t(57)=3.254, p=0.002) and of 91.4 grams (24.3%) in the ZOTRIM and fibercondition combined (t(57)=5.757, p<0.001). The reduction in intake of19.1 gram (5.1%) from control in the inulin only condition compared tothe control condition proved insignificant (p=0.188). Intake wassignificantly lower in the ZOTRIM and fiber combined condition versusthe ZOTRIM alone (t(57)=3.852, p <0.001) or fiber alone conditions(t(57)=4.624, p<0.001).

Energy Intake.

A 2×2 repeated measures ANOVA demonstrated a significant main effect ofZOTRIM on caloric intake (F(1, 57)=16.681, p<0.001). The ANOVA alsodemonstrated a significant main effect of inulin fiber on caloric intakeacross conditions, (F(1, 57)=13.366, p=0.001). There was no interactionbetween ZOTRIM and fiber conditions (F(1, 57)=0.193, p=0.662).

Paired samples t-tests showed there was a significant reduction incaloric intake from control of 132.2 kcal (17.6%) in the ZOTRIMcondition (t(57)=3.365, p=0.001), of 89.9 kcal (11.9%) in the fibercondition (t(57)=2.621, p=0.011) and of 202.4 kcal (26.9%) in the ZOTRIMand inulin fiber condition combined (t(57)=5.629, p<0.001). Caloricintake was significantly lower in the ZOTRIM and fiber combinedcondition versus the ZOTRIM alone (t(57)=2.504, p=0.015) or fiber aloneconditions (t(57)=3.178, p=0.002).

Analysis of the time taken to consume the ad-libitum lunch revealed asignificant main effect of ZOTRIM (F (1,57)=4.196, p=0.045). There wasno effect of inulin fiber (F (1,57)=0.010, p=0.921) and no interactionbetween ZOTRIM and inulin fiber (F (1,57)=3.316, p=0.074). Pairedsamples t-test showed there was a shorter lunch duration with ZOTRIMalone compared to placebo (t (57)=2.903, p=0.005).

Food Choice.

The twelve food items offered at the ad-libitum lunch were analyzedaccording to variation in fat content and taste. Foods offered weregrouped into high fat savory (HFSV), low fat savory (LFSV), high fatsweet (HFSW), low fat sweet (LFSW) sets, as shown in Table 8.

TABLE 8 HFSV LFSV HFSW LFSW flora bread Cookies Jelly Babies salamiturkey Chocolate Mousse Fruit Cocktail cheese snack a jacks crispscucumber

A four way within-subjects ANOVA was performed with taste(savory/sweet), fat (high/low), inulin fiber (present/not) and ZOTRIM(present/not) as within-subjects factors. Significant main effects oftaste (F (1,57)=10.457, p=0.002), fat (F (1,57)=90.637, p<0.001), inulinfiber (F (1,57)=9.775, p=0.003) and ZOTRIM (F (1,57)=23.944, p<0.001)were found on intake, but there were no significant interactions.Subsequent t-tests revealed that overall, gram intake of savory itemswas significantly greater than intake of sweet items (t (57)=3.234,p=0.002) and gram intake of low fat items was significantly greater thanintake of high fat items (t (57)=9.520, p <0.001).

There was a significant reduction in HFSV intake with inulin fiber andZOTRIM combined compared to placebo (t (57)=4.315, p<0.001) and comparedto inulin fiber alone (t (57)=3.127, p=0.003). For LFSV intake, therewas a significant reduction with ZOTRIM alone (t (57)=2.593, p=0.012)and with the ZOTRIM and inulin fiber combination (t (57)=2.470, p=0.017)compared to placebo. Intake of LFSV items was also significantly reducedfollowing ZOTRIM alone (t (57)=2.004, p=0.050) and ZOTRIM+inulin fibercombined (t (57)=2.036, p=0.046) compared to inulin fiber alone.

It was also found that gram intake of HFSW items was significantlyreduced with ZOTRIM alone (t (57)=2.207, p=0.031) and with ZOTRIM+inulinfiber combined (t (57)=5.099, p<0.001) compared to placebo. HFSW intakewas also significantly lower with ZOTRIM+inulin fiber combined versuswith ZOTRIM alone (t (57)=2.440, p=0.018) or inulin fiber alone (t(57)=3.146, p=0.003). No significant effects of ZOTRIM or inulin fiberwere found on gram intake of LFSW items.

Total Daily Intake.

Total daily intake, including calories from the product, breakfast andlunch was analyzed using a 2×2 repeated measures ANOVA. Thisdemonstrated a main effect of ZOTRIM on kcal intake (F (1,57)=16.681,p<0.001). There was no effect of inulin fiber (F (1,57)=1.880, p=0.176)and no interaction between inulin fiber and ZOTRIM (F (1,57),=0.193,p=0.662). Paired t-tests revealed that there was a significant reductionin kcal intake with ZOTRIM alone (t (57)=3.365, p=0.001) and with theinulin fiber and ZOTRIM combination (t (57)=4.238, p<0.001) compared toplacebo. It was also found that the kcal intake after ZOTRIM alone (t(57)=2.417, p=0.019) and after the combination of inulin fiber andZOTRIM (t (57)=3.178, p=0.002) was less than with inulin fiber alone.

Appetite.

Subjective parameters (hunger, gastric fullness, satisfaction, desire toeat, prospective consumption, thirst and nausea) rated on VAS wereanalyzed using within-subject ANOVA for repeated measures with conditionand time as within-subjects factors. Main effects of time were observed,as expected, reflecting changes in appetite ratings during the studydays. Trends for main effects of hunger and desire to eat were observedas well as a main effect for nausea.

Trend for a Main Effect of ZOTRIM on Hunger Ratings (F(1, 56)=2.865,p=0.096).

T-tests were used to investigate where the significant differences layand showed that compared to the control condition a significantreduction in ratings of hunger was found in the ZOTRIM and inulin fibercombined condition at the pre lunch time point, (t(57)=2.071, p=0.043),mean values: 61.02 mm versus 54.41 mm respectively). Furthermore,compared to the inulin fiber only condition a significant reduction inratings of hunger was found in the ZOTRIM and inulin fiber combinedcondition at the post lunch time point, (t(57)=2.770, p=0.008, meanvalues: 7.73 mm and 4.71 mm respectively).

Trend for an Interaction Between Fiber and Time on Desire to Eat (F(8,456)=1.870, p=0.063).

T-tests were used to investigate where the significant differences layand showed that, compared to the control condition, a significantreduction in ratings of desire to eat was found in the ZOTRIM and inulinfiber combined condition at the pre dose lunch time point, (t(57)=2.302,p=0.025, mean values=: 58.84 mm versus 51.29 mm respectively).Furthermore, compared to the control condition a significant reductionin ratings of desire to eat was found in the inulin fiber only conditionat the pre lunch time point, (t(57)=2.011, p=0.049, mean values: 61.19mm versus 55.26 mm respectively). Moreover, compared to the controlcondition a significant reduction in ratings of desire to eat was foundin the ZOTRIM and inulin fiber combined condition at the pre lunch timepoint, (t(57)=2.230, p=0.030, mean values: 61.19 mm versus 53.86 mmrespectively).

Significant Main Effect of Fiber on Nausea (F(1, 55)=6.203, p=0.016).

T-tests were used to investigate where the significant differences layand showed that compared to the control condition a significantreduction in ratings of nausea was found in the inulin fiber onlycondition 2 hours after breakfast time point, (t(57)=2.390, p=0.020,mean values: 9.50 mm versus 5.69 mm respectively). Furthermore, comparedto the ZOTRIM only condition there was a significant reduction in nauseain the inulin fiber only condition at the 2 hours after breakfast timepoint, (t(57)=2.584, p=0.012, mean values: 10.03 mm versus 5.69 mmrespectively). Furthermore, compared to the ZOTRIM and inulin combinedcondition there was a significant reduction in the inulin fiber onlycondition in ratings of nausea at the 2 hours after breakfast timepoint, (t(57)=2.053, p=0.045, mean values: 7.60 mm versus 5.69 mmrespectively). Moreover, compared to the ZOTRIM only condition there wasa significant reduction in ratings of nausea in the inulin fiber onlycondition at the pre dose lunch time point, (t(57)=2.040, p=0.046, meanvalues: 8.88 mm versus 5.97 mm respectively). In addition, compared tothe ZOTRIM only condition there was a significant reduction in ratingsof nausea in ZOTRIM and inulin fiber combined at the pre dose lunch timepoint, (t(57)=2.407, p=0.019, mean values: 8.88 mm versus 6.00 mmrespectively).

Example 3: Animal Model for Food Intake

Studies are conducted with male Sprague-Dawley rats weighing 270-290grams. Three days before the start of an experiment, the animals areweighed and individually housed. Normal rat chow pellets and tap waterare present ad libitum and are provided by food troughs and drinkingspouts, which allow continuous recording of the food consumed.Compositions containing plant extracts+inulin are administered atpredetermined times to the treatment group. Food intake is recorded bycontinuously weighing the amount of food remaining in a round stainlesssteel food basket. Food intake is continuously or intermittentlyrecorded over the entire time of an experiment. The weight of eachanimal is determined on each day of the experiment and recorded,together with any unusual observations, e.g., stressed animals,difficulties with plant extract application, etc. Statistical analysisto detect differences in ingestive behaviour between the control groupand the treatment group is performed.

What is claimed is:
 1. A composition for suppressing appetite consistingessentially of about 336 mg of yerba maté leaf extract, about 285 mg ofguarana seed extract, about 108 mg of damiana leaf extract, about 5grams of isolated, fermentable inulin, vitamin B and vitamin C.
 2. Thecomposition of claim 1, wherein said composition is formulated as asachet, solid food product, dairy product, breakfast cereal, muesli,candy, confectionary, cookie, biscuit, cracker, chocolate, chew, chewinggum, dessert, powdered drink or liquid comestible.